Researchers Discover New Way Gene Defects Can Lead to Cancer

By HAROLD M. SCHMECK Jr.

Published: June 22, 1989

Scientists have found a previously unknown way in which gene defects can lead to cancer, a discovery that may eventually offer improved ways of detecting some forms of cancer in the earliest stages when treatment can be most effective.

The research showed evidence of a class of cancer-promoting genes that function in an unexpected way, said Dr. Ronald M. Evans of the Salk Institute for Biological Studies, in La Jolla, Calif. The genes inactivate other genes that would ordinarily prevent the cancer process from starting, he said.

''I believe it is a new transforming principle,'' said Dr. Evans. In transformation, cells lose their normal controls over growth and become cancerous. The research by Dr. Evans, Dr. Klaus Damm and Dr. Catherine C. Thompson, all of the Salk Institute, is reported in the issue of the journal Nature being published today.

Scientists at Princeton and Johns Hopkins universities have discovered a similar effect that is produced by a different cancer-related gene that is believed to play a role in colon cancer. Genes' Role in Cancer

In the past decade, scientists have discovered several dozen genes in human tissues that contribute to cancer formation when they become abnormal or are abnormally activated. In many cases they are abnormal versions of genes that have natural functions in orchestrating the growth and proliferation of tissues. The genes that contribute to cancer are called oncogenes.

Specialists have demonstrated that there are two types of oncogenes. Those of one type, dominant oncogenes, contribute directly to excessive and unregulated growth of cells. A more recently discovered class, recessive oncogenes, actually protect against abnormal cell growth.

Cancers develop only when the patient's cells lose all the protective effect because both copies of the normal gene are either lost or have become changed enough to make them ineffective.

Laboratory experiments by Dr. Evans's group, as well as the research at Princeton and Johns Hopkins, have produced evidence that a third class of oncogenes exists. Such oncogenes appear to be capable of inactivating normal genes that would ordinarily keep cell growth under control. Third Type of Oncogene

The scientists at Salk found this unexpected type of activity in an oncogene called v-erbA. This gene is an aberrant version of a normal gene that is the blueprint that cells use to produce the receptor for thyroid hormone. A hormone receptor is a chemical structure, either within a cell or on its surface, to which the hormone must attach to produce its normal effects on the cell.

Thyroid hormone's major known functions are to increase the production of proteins in the body and to increase cells' oxygen consumption. Recent studies suggest that another important function of the hormone is to induce blood cells to evolve from their immature, rapidly growing, stage into mature cells, Dr. Evans said. The process is called differentiation.

In their laboratory experiments, his group found that the protein for which the v-erbA oncogene is the production blueprint couples with normal thyroid hormone. The combination then prevents the activation of particular segments of the genetic material DNA, or deoxyribonucleic acid. Ordinarily those segments of DNA would act as genes to promote the proper evolution of cells responsive to thyroid hormone, including blood cells. 'Important Implications'

''These results have important implications for the mechanism of action of thyroid hormones as well as oncogenesis,'' said the report in Nature.

The new research suggests that the v-erbA gene blocks the normal actions of thyroid hormone in helping immature cells differentiate. This blockage could then lead to the production of large numbers of abnormally immature blood cells, and conceivably other cells as well.

Dr. Evans said it was too early to tell how widespread the third category of oncogenes may be in human cancers.

He said the discovery of the role of v-erbA in test-tube studies might eventually lead to the development of diagnostic tests in which the presence of copies of the gene in human tissues would be used as evidence that the cancer process is beginning.

Similar tests have already been developed to aid in early diagnosis of patients at high risk of developing a rare cancer of the eyes called retinoblastoma.